Table 2 Summary of studies included in the review by outcome of interest

Elafros (2017) [35]

Zambia

Prospective observational cohort study (N = 145)

Patients on both HAART and AED

Adherence at 6 months

Suboptimal adherence at 6 months with 18 out of 33 (56%) participants on HAART experiencing more than 1 week lapse in AED supply. At 2 weeks, a greater proportion of participants on HAART and EI-AED participants reported increased nausea or vomiting compared with baseline (p < 0.05).

Knight (2015) [36]

South Africa

Prospective cohort study (N = 22)

HIV+ pregnant women with SJS/TEN

Maternal outcome for both the mother and fetus

Nevirapine was the offending drug in 21/22 (95%) cases. TEN was associated with poorer fetal outcomes. SJS/TEN-associated mortality is not increased in HIV+ pregnant women. Maternal SJS/TEN does not seem to commonly manifest in the fetus.

Saka (2013) [37]

Benin, Burkina Faso, Central African Republic, and Togo

Retrospective cross-sectional multicentric study (N = 177)

Patients with SJS/TEN of which 69% were HIV

SJS/TEN

Sex ratio (M/F) was 0.6, and the drugs responsible for SJS/TEN were dominated by antibacterial sulfonamides (38.4%) and nevirapine (19.8%), followed by tuberculosis drugs (5.6%).

Irungu (2017) [38]

Kenya

Cross-sectional study (N = 115)

Patients with severe cutaneous reactions

SJS/TEN

Females represented 59.1% of patients. The most common drugs implicated were sulfonamides (26.1%) and nevirapine (15.7%).

Kannenberg (2012) [39]

South Africa

Prospective observational cohort study (N = 75)

Patients admitted with TEN/SJS

SJS/TEN

Most patients with TEN/SJS were HIV+ (n = 59) and female (n = 51). Cotrimoxazole (24%) and nevirapine (29.3%) were the most common precipitants of TEN/SJS.

Dube (2013) [40]

South Africa

Retrospective study (matched case control study) (N = 36 of which 6 cases and 30 controls)

HIV+ pregnant women taking nevirapine-based regimens

SJS

Pregnancy increased the chances of developing SJS 14-fold (OR 14.28; 95% CI 1.54–131.82).

Marazzi (2006) [41]

SSA

Retrospective observational cohort study (N = 703)

HIV+ pregnant women treated with nevirapine-based regimens

SJS

Nevirapine-containing regimens in pregnant woman appear safe with only 1.1% developing SJS.

Noubiap (2018) [42]

SSA

Meta-analysis of 177 studies (N = 294,063)

General population and HIV+ on HAART

Dyslipidemia

Prevalence of dyslipidemia based on total cholesterol concentrations (25.47%; 95% CI 19.41–32.03%) (N = 6527), HDL cholesterol (45.6%; 95% CI 34.11–57.30%) (N = 5590), LDL cholesterol (24.30%; 95% CI 14.71–35.38%) (N = 5671), and triglycerides (19.68%; 95% CI 14.77–25.09%) (N = 6766).

Omo-Aghoja (2016) [43]

Nigeria

Matched case control nested within a cohort study (N = 154 pregnant women; N = 151 non-pregnant)

Pregnant HIV+ women

Dyslipidemia

Higher mean of very-low-density lipoprotein mg/dl was reported in pregnant women 67.79 (SD 162.75) versus non-pregnant women (p = 0.045).

Mehta (2019) [44]

South Africa

Prospective observational cohort study (N = 10,417 of which 4013 were HIV+)

Infants born to HIV+ women on nevirapine-based regimens in the first trimester

Congenital malformation

First trimester exposure to nevirapine was associated with an increased risk of CM (risk ratio 9.28; 95% CI 2.3–37.9) compared to births not exposed to ART in the first semester. CM rates in births exposed to efavirenz during the first trimester were similar to births not exposed to HAART (RR 0.87; 95% CI 0.12–6.4).

Liu (2014) [45]

South Africa/Zambia

Prospective observational cohort (N = 600)

Infants born to HIV+ women on HAART

Congenital malformation

Overall CM at delivery detected was 6.4% in South Africa and 5.6% in Zambia.

Raesima (2019) [46]

Botswana

Birth outcomes surveillance study (N = 3076)

Infants born to HIV+ women on dolutegravir-based regimens

Congenital malformation

A slightly higher prevalence of neural-tube defects among deliveries in HIV+ mothers who had been taking dolutegravir at the time of conception than among deliveries in which the mothers were HIV− (< 1%).

Zash (2019) [47]

Botswana

Birth outcomes surveillance study (N = 1683 deliveries)

Infants born to HIV+ women on dolutegravir-based regimens

Congenital malformation

Difference of prevalence of 0.20% (95% CI 0.01–0.59) in neural-tube defects among deliveries when dolutegravir is taken at conception compared to non-dolutegravir-based HAART. Also, there were major external structural defects observed in 0.95% of deliveries among women exposed to dolutegravir at conception versus 0.68% in women not exposed to dolutegravir.

Ekouevi (2011) [48]

West Africa

Retrospective cross-sectional study (N = 344)

Pregnant HIV+ women on efavirenz- or nevirapine-based regimens during the first trimester of pregnancy

Congenital malformation

No visible congenital malformation was observed in women exposed to efavirenz or nevirapine.

Gibb (2012) [49]

Uganda/Zimbabwe

RCT (N = 382 pregnancies)

Pregnant HIV+ women on tenofovir-based regimens

Congenital malformation

No increase in congenital, renal, or growth abnormalities was observed with in utero tenofovir exposure.

Ford (2010) [50]

Global/SSA

Meta-analysis with 12 studies (N = 9835)

Pregnant HIV+ women on efavirenz-based regimens during the first trimester of pregnancy

Congenital malformation

No differences in overall risks of CM between women on efavirenz versus non-efavirenz-containing regimens during the first trimester of pregnancy (relative risk 0.78, 95% CI 0.56–1.08).

Baynes (2019) [51]

SSA

Meta-analysis of 15 studies (N = 86,879)

HIV+ patients on HAART

Prevalence of CKD

Overall pooled prevalence was 6.42% (95% CI 5.2–7.6%), and the majority of patients with CKD were diagnosed with stage 3.

Mtisi (2019) [52]

SSA

Systematic review of 31 studies (N = 106,406)

HIV+ adults on tenofovir-based HAART

Decline of renal function

Some studies reported statistically significant renal function decline, but the clinical significance of this effect was not enough to contraindicate its continued use in HAART regimens.

Cassidy (2019) [53]

Botswana

Prospective observational cohort study (N = 493)

Pregnant HIV+ women on efavirenz-based regimens

Neurodevelopmental outcomes

Adjusted mean scores for the efavirenz-exposed group were poorer compared to the efavirenz-unexposed group on Bayley-III Receptive Language (21.5 versus 22.5, p = 0.05), Developmental Milestones Checklist Locomotor (30.7 versus 32.0, p < 0.01), Fine Motor scales (17.8 versus 19.2, p < 0.01), Profile of Social Emotional Development (11.7 versus 9.9, p = 0.02), and Developmental Milestones Checklist Language scale (17.6 versus 16.5, p = 0.01).

Chaudhury (2018) [54]

Botswana

Prospective study nested within one observational cohort and one interventional (N = 598)

HIV exposed and uninfected children exposed in utero to HAART versus zidovudine monotherapy

Neurodevelopmental outcomes

Neurodevelopmental outcomes at 24 months of age were similar in maternal HAART exposed versus zidovudine exposed HIV exposed uninfected children.

Chaudhury (2017) [55]

Botswana

Prospective observational cohort study (N = 670)

In utero HIV-exposed uninfected children, of which 36% were exposed in utero to maternal HAART and 64% to zidovudine

Neurodevelopmental outcomes

No evidence suggesting an adverse impact of in utero HIV and maternal HAART exposure on early age neurodevelopment.

Wedderburn (2019) [56]

South Africa

Prospective observational cohort study (N = 1225)

HIV-exposed uninfected children on HAART

Neurodevelopmental outcomes

Uninfected children exposed to maternal HIV infection and HAART have increased odds of receptive and expressive language delays at 2 years (aOR 1.96, 95% CI 1.09–3.52; aOR 2.14, 95% CI 1.11–4.15, respectively).

Kacanek (2018) [57]

Botswana

RCT (N = 197)

HIV-exposed uninfected children with in utero exposure to NRTI containing HAART

Neurodevelopmental outcomes

Neurodevelopmental outcomes in 24-month-old HIV-exposed uninfected children of HIV+ mothers with baseline CD4 ≥ 200 were similar in those randomized to a dual–NRTI + protease inhibitor-based compared to a triple-NRTI-based HAART regimen.